Inhibition of Partially Purified Rat Brain Na+, K+- Dependent Atpase by Bile Acids, Phenolic Acids and Endotoxin

Abstract

Sera from patients with fulminant hepatic failure (FHF) contains substance(s) which inhibit leukocyte ouabain-sensitive Na efflux and rat brain Na+,K+-dependent ATPase in vitro. Similar effects in the patients could be an important mechanism in the development of encephalopathy and cerebral edema. Bilirubin, free fatty acids and mercaptans inhibit Na+,K+-ATPase in vitro. The effects of a number of other potentially toxic substances present in the serum of patients with FHF is studied. Chenodeoxycholic acid, p-hydroxyphenyllactic acid, p-hydroxyphenylpyruvic acid and endotoxin caused 30-45% inhibition of partially purified rat brain Na+,K+-ATPase at concentrations known to occur in the serum of patients with FHF. At low concentrations the inhibitory effects of these substances were additive, but at higher concentrations a maximum level of inhibition was reached. These further substances are likely to be important in the disturbances of brain function found in FHF.